Method and apparatus utilizing heart sounds for determining pressures associated with the left atrium

ABSTRACT

Non-invasive apparatus and method for obtaining a quantitative determination of mean left atrial transmural pressure or otherwise obtaining a quantitative determination of a left atrial pressure value. A balloon is inserted by means of a catheter into the esophagus and positioned adjacent the left atrium. The balloon is gradually inflated. A tracing of mean balloon pressure is obtained as the balloon is inflated. In addition, a tracing of balloon pressure on a steady baseline and with low frequency oscillations due to respiration filtered out is obtained whereby the tracing represents balloon pressure oscillations effected by left atrial pressure. In accordance with the oscillometric principle the mean balloon pressure is measured when the intensity of a sound wave, after its transmission through the balloon, is at a peak. This mean balloon pressure, after adjustment for the effect, if any, of heart weight, is indicative of approximate mean left atrial pressure. Mean left atrial transmural pressure may be determined by adjusting for the effects of heart weight and intrapleural pressure on mean pressure at peak sound intensity by subtracting therefrom the balloon pressure at which balloon volume begins to increase greatly relative to the increase in balloon pressure.

This is a continuation-in-part of U.S. patent application Ser. No.08/114,775, filed Aug. 31, 1993, now U.S. Pat. No. 5,398,692, which is acontinuation of U.S. patent application Ser. No. 07/980,460, filed Nov.23, 1992 (now U.S. Pat. No. 5,263,485), which is a continuation-in-partof U.S. patent application Ser. No. 07/717,854, filed Jun. 25, 1991 (nowU.S. Pat. No. 5,181,517), which is a continuation-in-part of U.S. patentapplication Ser. No. 07/409,041, filed Sep. 18, 1989 (now U.S. Pat. No.5,048,532). The disclosures thereof are hereby incorporated herein byreference.

TECHNICAL FIELD

The present invention relates generally to the quantitativedetermination of a pressure within a body with particular application toobtaining quantitative pressure values for determining mean left atrialpressure as well as mean left atrial transmural pressure and otherpressures associated with the left atrium.

BACKGROUND ART

Ever since the English scientist Stephen Hales first measured the bloodpressure by observing the blood rise in a tube inserted in an artery ofa horse in 1733, scientists and physicians have sought better ways tomeasure blood pressure in people.

An instrument in common use for indirectly measuring blood pressure is asphygmomanometer, which comprises an inflatable cuff which wraps aroundthe upper arm above the elbow, a rubber bulb to inflate the cuff, and adevice to measure the levels of pressure. It is well known that if thecuff is inflated to above systolic pressure, then slowly decompressed,oscillations corresponding to the heart rate will appear in the cuffpressure beginning somewhat above systolic pressure. These oscillationstypically reach a maximum amplitude and then diminish until they arelost. The French physiologist, E. J. Marey, who discovered thisphenomenon in 1876, reasoned that the peak amplitude of oscillationoccurred close to mean arterial pressure. This hypothesis was confirmedby later investigators, and various methods of blood pressuredetermination based on the "oscillometric principle" were subsequentlydeveloped.

In 1905, Dr. N. S. Korotkoff proposed an auscultatory method ofdetermining blood pressure. In this method, an arm cuff is inflateduntil it stops the circulation of blood beyond the cuff. Thereafter, astethoscope is used to listen to the artery just distal to the cuff.Korotkoff hypothesized that the first sounds heard when the arm cuff isslowly deflated correspond to maximum pressure, whereas minimum pressureoccurs when the sounds disappear. Later laboratory and clinical studiesconfirmed the accuracy of the auscultatory method, which eventuallybecame universally adopted in clinical medicine.

The above techniques have heretofore been considered to provideinsufficiently precise measurements for adequate management of cardiacpressures in critically ill patients. It has also not been possible tonon-invasively determine left ventricular preload, which heretofore hasbeen determined invasively by measuring the mean left atrial pressure orthe pulmonary capillary wedge pressure.

In 1953, Lategola and Rahn demonstrated the efficacy of a flow-directedpulmonary artery catheter for the direct measurement of pulmonary arterypressure. Lategola and Rahn, A Self-Guiding Catheter for Cardiac andPulmonary Arterial Catheterization and Occlusion, 84 Proc. Soc. Exp.Biol. Med. 667-668 (1953). In 1970, Swan, Ganz, and associates reporteduse of a flow-directed catheter in humans and further refined it forclinical use and for the direct measurement of pulmonary capillary wedgepressure. Swan, Ganz, Forrester, Marcus, Diamond, and Chonette,Catheteriztion of the Heart in Man with Use of a Flow-DirectedBalloon-Tipped Catheter, 283:9 The New England J. Med. 447 (1970). Atpresent, this catheter is an invaluable aid in the management ofcritically ill patients with pulmonary and cardiac disease, and thepulmonary wedge pressure (as an estimation of mean left atrial pressureor left ventricular filling pressure, commonly referred to as preload)is the standard of reference for intravascular volume management.

Numerous potential indications for pulmonary artery catheterization arenow accepted. For example, catheterization is widely used in theevaluation and management of patients with acute myocardial infarction,for patients in shock, in the recognition of hypovolemia, in thetreatment of patients suffering respiratory failure with persistenthypoxemia, and in patients with congestive heart failure.Catheterization is especially useful in assessing cardiac function insurgical patients, both pre-, intra-, and postoperatively. Since 1970,the ability to measure pulmonary capillary wedge pressure and cardiacoutput with the flow-directed catheter has resulted in the developmentof bedside hemodynamic monitoring, a procedure now performed daily inmost hospitals in the United States. J. M. Gore et al., Handbook ofHemodynamic Monitoring, 3 (1985). Since the introduction of theSwan-Ganz catheter in 1970, it is reported that several millionpulmonary catheters have been placed in patients with acute myocardialinfarction. Gore et al., 92:4 Chest, 712 (October 1987).

Despite the widespread use of the pulmonary artery flow-directedcatheter, the procedure is not without drawbacks. Complications that mayarise from use of the catheter include pulmonary artery thrombosis orembolus, knotting of the catheter, rupture of the balloon and/or of apulmonary artery, pulmonary hemorrhage, pneumothorax, hemothorax, rightatrial thrombosis, sepsis, internal jugular stenosis or thrombosis,atrial and ventricular arrhythmias, electromechanical dissociation,right-sided endocardial lesions, and right-sided endocardial infection.Robin, The Cult of the Swan-Ganz Catheter, Overuse and Abuse ofPulmonary Flow Catheters, 103:3 Annals of Internal Medicine 445(September 1985). In recent years, the safety and efficacy of pulmonaryartery catheterization has become a subject of increased scrutiny andconcern. One study suggests that flow-directed pulmonary arterycatheterization may predispose patients to the development ofright-sided endocarditis. Rowley, Clubb, Smith, and Cabin, Right-SidedInfective Endocarditis as a Consequence of Flow-DirectedPulmonary-Artery Catheterization, 311:18 The New England J. Med. 1152(Nov. 1, 1984). The medical literature abounds with articles addressingthe numerous medical complications associated with pulmonary arterycatheterization. See, e.g., Murray, Complications of InvasiveMonitoring, 15:2 Medical Instrumentation 85 at p. 89, March-April 1981,which lists various references related thereto. Perhaps the most seriousallegation to date is that complications associated with the use of thepulmonary artery catheter in patients with acute myocardial infarctionhave resulted in an unusually and unacceptably high mortality rate.Robin, Death by Pulmonary Artery Flow-Directed Catheter, Time for aMoratorium? (editorial), 92:4 Chest 727 (October 1987).

In addition to the safety concerns, there is a relatively high monetarycost of critical care invasive monitoring, which cost may be minimizedby the availability of a non-invasive procedure where indicated. Thus, aneed has existed for a non-invasive and less costly improved method foraccurately measuring blood pressure in the left atrium in people.

Invasive hemodynamic measurement nevertheless remains an important andfeasible adjunct to clinical practice. Successful monitoring permitsaccurate determination of the state of the diseased heart and providesguidance for treatment and intervention to alter the course of a varietyof diseases. It is recognized that modern Swan-Ganz catheters allow forthe measurement of cardiac output, oxygen consumption, continuous mixedvenous oxygen saturation, and cardiac pacemaking, and that manycritically ill patients will require this degree of sophisticatedmonitoring. Nevertheless, given the knowledge of mean left atrialpressure and left atrial transmural pressure alone, there are numerouspatients who could be safely managed in intermediate care units or onregular nursing floors. Certain patients undergoing general anesthesiacould also benefit from less invasive monitoring of mean left atrialpressures. Furthermore, a less invasive technique for the measurement ofmean left atrial pressure could be used to rationally screen patients todetermine whether or not they would benefit from Swan-Ganzcatheterization; otherwise, monitoring of mean left atrial pressure bysuch a less invasive technique may suffice to manage the patient outsidethe intensive care setting.

Thus, a long-felt need exists for a non-invasive method to accuratelydetermine mean left atrial pressure. This is a primary underlyingobjective of the present invention.

An esophageal catheter with a balloon having an inflated length anddiameter of 3.1 cm. and positioned adjacent the left atrium haspreviously been used in an attempt to provide the shape of the curve ofleft atrial pressure. See Gordon et al, Left Atrial, "Pulmonarycapillary", and Esophageal Balloon Pressure Tracings in Mitral ValveDisease, British Heart J., 18: 327-340, 1956.

In order to record left atrial events, Gordon et al suggests, at page330, that the esophageal balloon to be positioned adjacent the leftatrium must be relatively small, "otherwise the tracings will bedistorted by pressure or volume changes taking place at other than thedesired left atrial level" and that it was "usually necessary to suspendrespiration while the records were being made."

However, Gordon did not provide pressure measurement and, indeed, statedthat his system was incapable of obtaining left atrial pressure values.Thus, Gordon et al states, at page 330, that "no attempt was made tomeasure absolute pressures from these tracings, as the amplitude of thepressure pulse is a function of the elasticity of the system, the amountof fluid in the balloon and the initial pressure within it, as well asthe intra-atrial pressure." As again indicated at page 338 of Gordon etal, one of the drawbacks of the Gordon et al system is the inability toobtain absolute left atrial pressure values. That was more than 30 yearsago.

A concern when attempting to pick up left atrial pressure waves usingballoon-tipped esophageal catheters is the problem of insuring that theballoon is properly positioned behind the left atrium. In connectionwith the placing of electrodes for trans-esophageal heart pacing, it hasbeen suggested that a positioning balloon may be inserted on the distalend of an esophageal catheter to anchor the catheter in the stomach.Since the distance between the left atrium and the stomach(gastroesophageal junction) is relatively constant in an adult, thepacing electrodes could then be affixed to the catheter at this distanceproximal to the stomach balloon. See Andersen et al, Trans-EsophagealPacing, PACE, Vol. 4, July-August, 1983, pp. 674-679. However, thisprocess is not suitable for use with non-adults since thegastroesophageal junction to left atrial distance will not be constantbut will vary for neonates and children. It has also been suggested, inconnection with observing the esophageal pulse in mitral valve disease,that an electrode may be used to position an esophageal balloon behindthe left atrium by attaching it to the catheter just above the balloonto measure the esophageal electrocardiogram from behind the left atrium.See Zoob, The Oesophageal Pulse in Mitral Valve Disease, British HeartJ., Vol. 16, 1954, pp. 39-48. Also see Brown, A Study of the EsophagealLead in Clinical Electrocardiography, American Heart J., Vol. 12, No. 1,July, 1936, pp. 1-45; and Oblath and Karpman, The Normal Esophageal LeadElectrocardiogram, American Heart J., Vol. 41, 1951, pp. 369-381.

While mean left atrial pressure is considered important, pulmonaryvenous transmural pressure or mean left atrial transmural pressure(hereinafter called "transmural pressure") is considered to be a moreclinically useful physiologic value because it allows physicians to moreprecisely determine when a patient could go into pulmonary edema fromheart failure or volume overload, and it also allows an assessment ofthe effect of positive end expiratory pressure with ventilated patients.For the purposes of this specification and the claims, transmuralpressure is equal to the difference between mean left atrial pressureand the intrapleural pressure. The tissue pressure in the chest(mediastinum) reflects the intrapleural pressure, which is usuallysub-atmospheric at end expiration during regular breathing while sittingerect. However, the transmural pressure has not been commonly used byphysicians because it has heretofore not been readily obtainable andavailable.

It is an object of the present invention to non-invasively obtainquantitative pressure measurements to readily determine a person's meanleft atrial pressure as well as the transmural pressure safely,accurately, and reliably. As used herein and in the claims, the terms"transmural pressure" and "pulmonary venous transmural pressure" aremeant to refer to the mean left atrial transmural pressure.

It is another object of the present invention to obtain suchmeasurements economically and easily.

It is a further object of the present invention to provide a method fordetermining a person's mean left atrial and transmural pressures whichmay be administered by a non-physician.

It is still another object of the present invention to non-invasivelyobtain quantitative pressure measurements to readily determine otherpressures associated with the left atrium safely, accurately, andreliably.

SUMMARY OF THE INVENTION

In order to non-invasively and readily determine a person's mean leftatrial and transmural pressures safely, accurately, and reliably, inaccordance with the present invention a balloon is inserted into theperson's esophagus and positioned adjacent the left atrium and inflated,and the mean balloon pressure is measured when the intensity of heartsounds, after they are transmitted through the balloon, is at a peak.This peak sound intensity is indicative of unloading of the balloon (orballoon fabric) due to the mean balloon pressure being equal to the meanpressure adjacent the balloon, i.e., a pressure effected by the person'smean left atrial pressure. This pressure, after adjustment, as discussedbelow, for the effects of the weight of the heart and of intrapleuralpressure, can be used to determine approximately the mean left atrialand transmural pressures.

The effects of heart weight and intrapleural pressure may be determinedby moving the balloon to or positioning another balloon at a position inthe esophagus away from where the heart presses on the esophagus and,while filling the balloon, noting the pressure at an initial slopechange (which represents approximately the intrapleural pressure). Thepressure contribution of heart weight may be calculated to be a pressureat an initial slope change as the balloon fills while behind the heartless the pressure at an initial slope change as the balloon fills whileaway from the heart. This pressure contribution is subtracted from themean balloon pressure at the peak sound intensity to obtain a moreprecise determination of mean left atrial pressure.

Transmural pressure, which is equal to the mean left atrial pressureless the intrapleural pressure, is as a result equal to the mean balloonpressure at the peak sound intensity less the pressure at the initialslope change. Thus, a determination of transmural pressureadvantageously does not require the movement of the balloon (or otherballoon) to a different location in the esophagus.

The above and other objects, features, and advantages of the presentinvention will be apparent in the following Best Mode for Carrying Outthe Invention when read in conjunction with the accompanying drawings inwhich like reference numerals denote the same or similar partsthroughout the several views.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 a side view of a combination of a balloon-containing catheter andan electrode-containing catheter in accordance with the presentinvention with the balloon inflated.

FIG. 2 is an enlarged side sectional view of the balloon of FIG. 1.

FIG. 3 is a partial left lateral sectional view of the human body takenalong the mid-sagittal plane and showing the balloon of FIG. 1 withinthe esophagus and adjacent the left atrium of the heart.

FIG. 4 is a front sectional view of the human body illustrating theposition of the heart.

FIG. 5.is a top sectional view of the human body, taken along lines 5--5of FIG. 4, at the level of the seventh thoracic vertebra and with theballoon of FIG. 1 in the esophagus.

FIG. 6 is a schematic view of apparatus, including theballoon-containing catheter of FIG. 1, which embodies the presentinvention.

FIG. 7 is a pressure trace of the left atrial pressure during onecardiac cycle as sensed by the balloon of FIG. 1 when adjacent the leftatrium.

FIG. 8 is a graph of an esophageal electrocardiogram of the left atriumduring one cardiac cycle.

FIG. 9 is a pressure trace of an unfiltered signal of balloon pressurewith respiratory and cardiac effected oscillations when the balloon ofFIG. 1 is adjacent the left atrium, as the balloon is graduallypressurized.

FIG. 10 is a pressure trace of mean balloon pressure for the pressuretrace of FIG. 1.

FIG. 11.is a pressure trace of amplified cardiac signal on a steadybaseline which signal is derived from the balloon pressure trace of FIG.9 and covers the same time period as that of FIGS. 9 and 10.

FIG. 12 is a graph of an electrocardiogram taken simultaneously with thepressure traces of FIGS. 9, 10 and 11.

FIG. 13 is a schematic view of an alternative embodiment of the presentinvention, it being understood that this embodiment is meant to includethe portion of apparatus of FIG. 6 which is connected to line 60.

FIG. 14 is a schematic view of apparatus, including the catheter of FIG.1, in accordance with another embodiment of the present invention.

FIG. 15 is a block diagram of electronic components for processing asignal provided by the apparatus of FIG. 14.

FIG. 16 is a pressure trace similar to that of FIG. 9.

FIG. 17 is a trace of amplified sound output from the apparatus of FIGS.14 and 15 and covering the same time period as that of FIG. 16.

FIG. 18 is a pressure trace similar to that of FIG. 11 which signal isderived from the balloon pressure trace of FIG. 16 and covers the sametime period as that of FIGS. 16 and 17.

BEST MODE FOR CARRYING OUT THE INVENTION

The use of the oscillometric principle to determine mean left atrialpressure or a pressure associated therewith by measuring mean pressurein an esophageal balloon gradually being inflated adjacent to the leftatrium when the amplitude of balloon pressure oscillations effected bythe left atrial pressure is at a peak is discussed in the aforesaid U.S.Pat. No. 5,263,485 and is discussed herein with reference to FIGS. 1 to13. The use of the oscillometric principle in accordance with thepresent invention to determine mean left atrial pressure or a pressureassociated therewith by measuring mean pressure in the balloon when theintensity of a sound wave, after it is transmitted through the balloon,is at a peak is discussed thereafter with reference to FIGS. 14 to 18.As applicable, the principles discussed with reference to FIGS. 1 to 13will apply to the present invention as discussed with reference to FIGS.14 to 18.

Referring to FIGS. 1 and 2, there is illustrated generally at 19catheter apparatus including a hollow catheter 20 comprising a length offlexible tubing 22 having a bore or lumen 23 and on one end of which isattached a balloon 24 for flow communication with the lumen 23 forpressurization of the balloon and for sensing the pressure thereof. Anelectrode 21 may be positioned just above the balloon 24 for obtainingan esophageal electrocardiogram and an electrical lead 25, within asecond catheter 27, provided thereto, as will be discussed in greaterdetail hereinafter.

Referring to FIG. 3, there is illustrated the placement of the balloon24 within the esophagus 26 of a human body for the purpose of sensingthe pressure of the left atrium 28 of the heart 30. The catheter 20 isinserted balloon first through nasal passage 32, pharynx 34, then intothe esophagus 26. If desired, the balloon may alternatively be insertedthrough the mouth. As shown in FIG. 3, the outer wall of the left atrium28 is adjacent and essentially in direct contact with the outer wall ofthe esophagus 26, and advantage is taken of this relationship todetermine mean left atrial pressure, transmural pressure, and associatedpressures by means of the balloon 24 thusly inserted non-invasively intothe esophagus 26 and positioned therealong adjacent the left atrium soas to be sufficiently affected thereby to sense left atrial pressure, aswill be discussed in greater detail hereinafter.

The tubing 22, which may have an inner diameter of perhaps approximately0.050 inch, and balloon may be composed of any suitable flexible,chemically inert, non-toxic material such as polyvinyl chloride forwithstanding operating pressures without significant expansion. Apreferred tubing is composed of an 83 to 85 durometer polyvinyl chloridesold by Colorite Plastics Co. of Richfield, N.J. and identified as itsUnichem polyvinyl chloride no. 8311 G-015. A preferred balloon materialis a 70 durometer polyvinyl chloride from the same source and identifiedas its Unichem polyvinyl chloride no. 7011 G-015. Alternatively, thetubing and balloon may be composed of a 90 durometer polyurethane suchas sold by Miles Incorporated of Pittsburg, Pa. as Texin 990Apolyurethane or sold by B.F. Goodrich of Cleveland, Ohio as Fstane 5810polyurethane. Another suitable tubing is a Tygon® brand polyvinylchloride tubing having an inner diameter of approximately 0.050" whichis a product of Cole-Parmer Instrument Co., 7425 North Oak Park Avenue,Chicago, Ill. 60648-9930, as shown on page 636 of the Cole-Parmer1989-90 Catalog. The tubing 22 has a suitable length which may beperhaps 80 cm. The tubing 22 may desirably have markings (not shown)along the length thereof to indicate distance therealong so that theballoon 24 may be initially positioned approximately adjacent the leftatrium 28. The tubing may contain a portion 18 which extends over thelength of the balloon 24 and a portion 15 which extends from theballoon. Portions 15 and 18 are connected by means of a stainless steelferrule 44 over which the tubing is press fit. The distal end of theballoon is closing by plugging by a cylindrical plug 42 of stainlesssteel or the like over which tubing portion 18 is press fit. At eachballoon end, a sleeve 43 is fitted over the tubing portion 18 to providea larger diameter for securing the balloon fabric. Each balloon end isthen sealed by surgical thread 38 and/or silicone cement. A plurality ofapertures 46 are provided in the tubing (portion 18) wall over adistance from the closed end 42 equal to less than the balloon length toprovide flow communication between the tubing 22 and the interior of theballoon 24 for inflating the balloon and for sensing pressure therein.The balloon 24 fits over the tubing portion 18 containing the apertures46 and is attached to the tubing 22 at end portion 42 and at ferrule orsecond portion 44 between which portions are the apertures 46, asillustrated in FIG. 2. Pressurization and sensing lines may be attachedat the end 40, which is opposite the balloon end 42, as will bediscussed in greater detail hereinafter.

However, other suitable means may be used for such attachment. Forexample, the balloon may be fixed over the end of a catheter the end ofwhich is plugged. The balloon 24 may be constructed of any suitableflexible non-toxic film which can withstand operating pressures withoutrupture or irreversible deformation. The balloon 24 may have a capacityof perhaps about 2 milliliters. When inflated within the pressure rangefor determining mean left atrial pressure, the balloon 24 takes on agenerally cylindrical shape, as illustrated in FIGS. 1 and 2. Thethickness of the material of which the balloon 24 is made is perhapsabout 0.0005". The balloon 24 should function properly in any rotationalorientation around the longitudinal catheter axis. The balloon 24 may,for example, be constructed of low density polyethylene film such asExtrel® SF brand polyethylene film, a product of Exxon Chemical Co.,Polymers Group, Division of Exxon Corp., 351 North Oakwood Road, LakeZurich, Ill. 60047-1562.

Alternatively, a catheter in accordance with the present invention maybe extruded with the balloon suitably fitted thereon such as by heatsealing or RF (radio frequency) welding for either polyvinyl chloride orpolyurethane materials. If the balloon and tubing are composed ofpolyvinyl chloride, UV (ultraviolet) welding is preferably employed. A40 percent barium sulfate stripe may be put in the resin for the tubingto make it radiation-opaque so that it may be picked up on x-rays.

Referring to FIGS. 4 and 5, it should be noted that the esophagus 26 issandwiched between the left atrium 28 and the vertebral column 48 sothat when the balloon 24 is positioned adjacent the left atrium 28 thevertebral column 48 acts similarly as an anvil for effective action ofthe left atrium pressure on the balloon 24 to affect the pressuretherein as will be described hereinafter. The esophagus 26 is flanked bythe left and right lungs 50 and 52 respectively. The aorta 54 ispositioned generally between the esophagus 26 and the left lung 50 andin proximity to the vertebral column 48, as shown in FIG. 5.

Referring to FIG. 6, there is illustrated generally at 56 apparatus forpressurizing the balloon 24 and for sensing the pressure therein. Forthe purpose of precisely positioning the balloon 24 adjacent the leftatrium 28, the balloon 24 is first statically filled with apredetermined quantity of perhaps 1.4 milliliter of air via syringe 58,with stop cock or valve 96 suitably open for passage of the airtherefrom through line 60 to tubing 22 to which line 60 is suitablyattached at the end portion 40.

The balloon pressure is transmitted from line 60 through line 62 tofour-way stop cock or valve 64 which transmits the pressure through line66 to one side 74 of the diaphragm 86 of a differential pressuretransducer 68 and through line 70 to filter 72. Transducer 68 may, forexample, be a Validyne model DP7 differential pressure transducerprovided by Validyne Engineering Corp., 8626 Wilbur Avenue, Northridge,Calif. 91324. Pressure from the filter 72 is transmitted through line 76and stop cock or valve 78 to the other side 80 of the transducer 68. Thetransducer 68 converts the net pressure signal acting on the diaphragm86 to an electrical signal which is transmitted through line 82 to afirst signal processor 84. Processor 84 may be any suitable conventionalelectronic signal processing circuit which amplifies and otherwiseprocesses and conditions the electrical signal representations ofpressure and communicates these signals to a display means 85 via line87. Display means 85 may be a digital display, a strip chart recorder, acathode ray tube, or any other suitable device for displaying orutilizing the signals from processor 84.

The balloon 24 will not only sense atrial pressure but will also recordnormal peristaltic waves from swallowing as well as pressure excursionsfrom normal breathing. Peristaltic waves are easily distinguished bytheir high amplitude (up to 100 cm of water) and relative infrequencyand can therefore be ignored. Respiratory excursions (typically from -10to +10 cm of water at frequencies of 0.1 to 0.8 Hertz) can interferewith left atrial pressure wave form and measurement. They are thereforefiltered out during signal processing as described hereinafter.

Filter 72 is a low pass mechanical filter such as, for example, a Nupro®micrometer needle valve connected as shown in FIG. 6, a product of NuproCompany of 4800 East 345th Street, Willoughby, Ohio 44094. Theunprocessed signal carrying both the higher frequency cardiac wave form(generally 1.5 to 9.0 Hertz) effected by left atrial pressure and thelower frequency respiratory wave form (generally 0.1 to 0.8 Hertz) goesdirectly to the first side 74 of the differential pressure transducer 68via line 66. An identical signal is also transmitted to the variablecontrol valve 72. By restricting an orifice (not shown) in filter 72, inaccordance with principles commonly known to those of ordinary skill inthe art to which this invention pertains, the balloon pressure wave isfiltered to selectively pass the lower frequency component, whichincludes respiratory artifact, through line 76 and valve 78 to the otherside 80 of the differential transducer 68, and the higher frequencycomponent is excluded. This in effect allows the respiratory artifactarriving almost in phase on both sides of the transducer diaphragm 86 tocancel itself out so that the cardiac wave form is recovered andoutputted as an electrical signal through line 82 to the first signalprocessor 84.

With the balloon inflated, it is precisely positioned adjacent the leftatrium 28 by moving it up or down the esophagus 26 by withdrawing orinserting the catheter 20 at the nose until a typical left atrialpressure wave form, illustrated at 88 in FIG. 7, is seen on the pressuretrace from the first signal processor 84. As previously discussed, thiswave form 88 comprises the balloon pressure signal with the lowerfrequency respiratory wave form filtered out. This wave form 88 may beconfirmed as being a typical left atrial pressure wave form bycomparison with a simultaneous esophageal electrocardiogram, illustratedat 140 in FIG. 8, which is electrocardio conventionalelectrocardiograph, illustrated at 92 in FIG. 6. Electrocardiogram 140is obtained by the use of a stainless steel electrode, illustrated at21, which is suitably attached to the catheter 20 just above the balloon24. However, the electrode 21 may be otherwise adjacent the balloon 24.For example, an electrode for this purpose could comprise conductivematerial on the surface of the balloon. An electrical lead 25 isattached to the electrode and extends within a second catheter 27 and toelectrocardiograph 92 for transmitting the signals picked up by theelectrode 21 for processing therein. The lead 25 may, for example, besilvered 30 AWG wire-wrapping wire provided by OK Industries, 4Executive Plaza, Yonkers, N.Y. 10701. The catheters 20 and 27 may beheld together by suitable securing means such as, for example,cyclohexanone glue 16. Alternatively, a double-lumen catheter ofpre-formed polyvinyl chloride may be used. The electrode 21 ispreferably in the shape of a ring which encircles catheter tubing 22 soas to insure that it will be suitably positioned without interference bytubing 22 for sensing left atrial electrical activity. In accordancewith conventional practice, it may be required that skin electrodes 94also be hooked-up to the subject. The wave form 140 is characterized bya wave portion (which heralds atrial depolarization) which reaches ahigh voltage and becomes bi-phasic with a sharp upstroke and shows anintrinsicold deflection. Thus, points A, C, and V, shown on wave form 88in FIG. 7, are three essential components of the left atrial pressurewave, and these points are known to correspond to points P, R, and Trespectively on the electrocardiogram 140 of FIG. 8 thus confirming thatthe wave form 88 is a typical left atrial pressure wave form.

When, as the balloon and esophageal electrode are moved up and down theesophagus, a typical left atrial wave form, similar to wave form 88, issensed on the pressure trace from the first signal processor 84, whichindicates that the balloon 24 is suitably positioned adjacent the leftatrium 28, the balloon 24 is then fixed in place by applying tape overthe catheter 20 and onto the upper lip just beneath the nose. Thedistinctiveness of this wave form, confirmed by use of electrode 21, maydesirably reduce the level of skill required for proper positioning ofthe balloon. Alternatively, a conventional surface or skinelectrocardiogram may be obtained, by use of electrodes 94 on thesubject's body and wired to electrocardiograph 92, for comparison withwave form 88 to determine when the balloon is correctly positioned.However, the use of the esophageal electrocardiogram 140 for thispurpose is considered preferable since it may provide a more distinctivewave form which is more easily recognized. The use of either theesophageal or skin electrodes for positioning the balloon isadvantageously suitable for use with the wide range of body size frompremature neonates to adult men.

Other means for suitably positioning the sensing balloon mayalternatively be used. For example, as illustrated in the aforesaid U.S.Pat. No. 5,263,485, a positioning balloon may be positioned on acatheter to contact the esophago-gastric junction at the stomach of anadult and a sensing balloon positioned on a separate catheter and at adistance from the positioning balloon which approximates the relativelyconstant distance in an adult between the esophago-gastric junction andthe left atrium. This distance is of course relatively constant inadults but not in premature neonates and infants. For another example,the sensing balloon may be positioned by use of an esophagealelectrocardiogram alone, as discussed in "Optimal Mode ofTrans-esophageal Atrial Pacing" by M. Nishimura et al, American J. ofCardiology, vol. 57, 1986, p. 791-796. In regard to pacing, this articlestates that "the point showing the largest unipolar atrial electrogramwas thus considered the optimal site of pacing for both bi-polar anduni-polar stimulation." The left atrium may be assumed to be 1 to 2 cm.distal to this point. Also see "Trans-esophageal Atrial PacingThreshold: Role of Interelectrode Spacing, Pulse Width and CatheterInsertion Depth" by D. Benson et al, American J. of Cardiology, 1984, p.63-67.

As previously discussed, the pressure wave form 88 is insufficient fordetermining mean left atrial pressure due to its amplitude being afunction of the elasticity of the system, the amount of gas in theballoon, and the initial pressure within it, as well as the intra-atrialpressure and the surrounding tissue pressure. With the balloon 24precisely positioned, processing can begin for accurately andnon-invasively determining the mean left atrial and transmural pressuresor other pressures associated with the left atrium, as discussedhereinafter.

After proper placement has been accomplished, sensing balloon 24 isinitially evacuated to perhaps -10 to -12 cm of water pressure, lessthan the minimum expected pressure to be measured using syringe 58, withthe stop cock 96 open thereto. This purges the system of any gas, priorto beginning a measurement, to insure consistency, accuracy, andreliability of pressure measurements. The system is similarly alsopurged of any residual gases between measurements.

After the balloon 24 has been properly placed adjacent the left atrium28 and evacuated, it is gradually inflated with air or another suitableinert gas such as, for example, nitrogen gas or a suitable liquid suchas, for example, water for the purpose of determining mean left atrialpressure as hereinafter described. The use of a liquid may provideenhanced gain. If a liquid is used, it may be provided to line 60 bymeans of a liquid-filled syringe to which is attached a suitablemechanical or hydraulic pressurization device. The use of air maysimplify the equipment and its use and may therefore be preferred forthis purpose. A source of air under a sufficient pressure such as, forexample, 40 psig for inflating the balloon 24 is illustrated at 100.With stop cocks or valves 96 and 102 opened to connect the metering gassupply valve 98 with the line 60 and with syringe 58 closed to line 60by valve 96, the gas from source 100 is routed through line 104 to themetering valve 98 where it is released to line 106 and through stopcocks 102 and 96 and line 60 to catheter 20 in metered quantity forgradually inflating the balloon 24. As used herein and in the claims,the term "line", unless otherwise specified, is meant to refer totubing, a catheter, an electrically conductive wire, or other suitablemeans for transmitting a pressure or electrical signal. Valve 98 is aNupro® brand micrometer needle valve, a product of Nupro Company of 4800East 345th Street, Willoughby, Ohio 44094, which is constructed to allowa broad range of near constant flow rates against back pressures to amaximum of about 50 cm water (0.74 psi). It is precalibrated to providegas flows up to about 4 milliliters per minute on average. Othersuitable valves may alternatively be provided. Metering valve 98 is thusopened to provide a suitable gas flow such as a flow of approximately1.0 milliliter per minute for gradually filling the sensing balloon 24at a constant rate.

Alternatively, the balloon may be filled by a syringe that is controlledby a stepping motor and that employs a restricted orifice between thesyringe and line 60 so as to isolate the syringe from the line with amechanical low-pass filter.

While not wishing to be bound by theory here or elsewhere in thisspecification, the following is believed to occur as the sensing balloon24 is pressurized. The gradual filling of the sensing balloon 24 causesthe pressure therein to increase at a generally slow steady rate which,in accordance with the theory of the previously discussed oscillometriceffect, is affected by the atrial pressure causing oscillations thereinas well as by respiratory waves. As the mean balloon pressure approachesthe mean left atrial pressure, the atrial pressure oscillations ofballoon pressure increase in intensity or amplitude until the balloonpressure resonates maximally, i.e. reaches a peak amplitude, when themean balloon pressure approximates the mean left atrial pressure.Thereafter, as the mean balloon pressure continues to increase, theamplitude of oscillations due to the atrial pressure decreases. Morespecifically, the balloon pressure oscillates maximally when itsexpansion has increased the pressure in the tissue surrounding the leftatrium to the point where the mean tissue pressure equals mean leftatrial pressure (MLAP). Thus, it may be said that the balloon works bestas a pressure transmitter when it is unloaded, i.e., when the meanpressure on both sides of the balloon wall are equal, resulting in thegreatest amplitude of balloon pressure oscillations when the meanballoon pressure equals mean left atrial pressure.

FIGS. 9 to 12 are illustrations of four electronic displays or tracingsused to record and display the absolute balloon pressure wave form 108(FIG. 9), the mean balloon pressure wave form 110 (FIG. 10), thedifferential signal 112 with added gain from the signal processor 84(FIG. 11), and a simultaneous electrocardiogram 114 (FIG. 12). Verticalline 116 in each of FIGS. 9 to 12 represents the same point in time. Acomparison of the electrocardiograms 140 and 114 in FIGS. 8 and 12respectively indicates that the time scale for FIGS. 7 and 8 is greatlyexpanded relative to the time scale for FIGS. 9 to 12, i.e., the waveform 140 in FIG. 8 covers a period of about a second, and a multitude ofsuch waves over a multitude of seconds is shown in FIG. 12.

The absolute balloon pressure wave form 108 is obtained from a suitabletransducer 118 connected to line 60 via line 120. The transducer 118may, for example, be a Cobe CDX III transducer provided by CobeLaboratories, Inc., 1185 Oak Street, Lakewood, Co. 80215. The transducer118 converts the balloon pressure signal in line 120 to an electricalsignal which is transmitted through line 122 to second signal processor124, which is a suitable conventional electronic signal processingcircuit which suitably processes and conditions the electrical signalrepresentations of pressure and transmits these signals to a suitabledisplay means 142, which may be similar to display means 85, via line144. The processor 124 amplifies the signal for display as shown bytracing 108 in FIG. 9. Signal processor 124 also suitably processes thesignal, in accordance with principles commonly known to those ofordinary skill in the art to which this invention pertains, to providean electronic mean thereof as shown by tracing 110 in FIG. 10. Thetransducer 118 is referenced to one atmosphere of pressure absolute.

It should be recognized that other suitable analog or digital electronicsignal processing means can be employed to filter, amplify, compare, andotherwise process the signals. Both pressure transducers 68 and 118 aresuitably calibrated against a water manometer prior to use.

A suitable relief valve 130 is provided in line 60 to protect the system56 and the patient from over-pressurization. The relief valve 130 is setto open at a suitable pressure of perhaps 50 mm of mercury pressure tovent the tubing and balloon to atmosphere in order to preventdangerously high pressure such as might cause the balloon to rupture.

The absolute balloon pressure wave form 108 is comprised of lowamplitude high frequency oscillations effected by left atrial pressurewhich are superimposed on high amplitude low frequency respiratoryoscillations which are in turn super-imposed on the gradual increase inballoon pressure provided by gas supply valve 98. The mean balloonpressure wave form is shown at 110 in FIG. 10. By "mean balloonpressure" is meant, for the purposes of this specification and theclaims, the balloon pressure at the mean of each of the high frequency(greater than about 0.8 Hertz) oscillations. Stated another way, the"mean balloon pressure" wave form 110 is the absolute balloon pressurewave form 108 with the high frequency oscillations removed therefrom.When a signal is filtered, waves which are removed therefrom do notappear in the output while those which are passed or extracted do appearin the output. The abrupt slope change indicated at 200 from a fast to aslowed rate of pressure increase is indicative of the equalization ofballoon pressure with the surrounding tissue pressure prior to balloonexpansion.

The differential signal 112 is provided by the signal processor 84 afterlow frequency oscillations representing the respiratory artifact arefiltered out by the differential pressure transducer 68 so that the leftatrial pressure wave form is recovered. In addition, the rising absolutepressure due to the gradual inflation of the balloon 24 (which istreated by the filter 72 similarly as a low frequency oscillation andthus passed to transducer side 80) is also cancelled out by thedifferential transducer 68 so that the pressure signal 112 processed bysignal processor 84 is on a steady base line. The signal 112 is thenfurther filtered electronically, amplified, and displayed by the signalprocessor 84 on display 85.

Wave form 112 may alternatively be obtained by electronically invertingthe mean balloon pressure wave form 110 and adding the inverted waveform to the absolute balloon pressure wave form 108 and amplifying theoscillations obtained.

The use of a bias balloon 150 for alternatively eliminating respiratoryartifact to obtain signal 112 is illustrated in FIG. 13. The pressure inballoon 24 is transmitted through lines 60, 62, and 66 to one side 74 ofdifferential pressure transducer 68 similarly as illustrated in FIG. 6.This pressure, which is also transmitted through line 120 to transducer118 and converted to an electrical signal which is processed anddisplayed on display 142, includes the effects of respiratory artifactas well as atrial pressure. The bias balloon 150, similar to balloon 24and similarly inserted by means of a catheter 152, which may be similarto or a part of catheter 20, may also be pressurized via line 60 ashereinafter discussed. Bias balloon 150 is inserted into the esophagusintermediate the position of the left atrium and the nasal or mouthpassage, i.e., perhaps 10 or 11 cm. or more above the position ofballoon 24, so that the pressure therein is not affected by left atrialpressure. But bias balloon 150 does sense respiratory artifact, i.e.,pressure swings generated by respiration, and therefore may be said toreflect esophageal pressure and thus record the respiration inducedfluctuation in esophageal pressure. The bias balloon pressure istransmitted through lines 154 and 156 to the other side 80 ofdifferential pressure transducer 68. Thus, a pressure effected byabsolute left atrial pressure plus respiratory artifact is applied toone side 74 of transducer 68, and a pressure effected by respiratoryartifact is applied to the other side 80. The difference, representativeof left atrial pressure without the respiratory artifact, is outputtedas an electrical signal through line 82 to signal processor 84 whichtransmits a suitably processed signal of the resulting difference wavethrough line 87 to signal display 85, which may be similar to display142. One advantage of bias balloon 150 is that its use will eliminaterespiratory artifacts regardless of their frequency. If desired, thebias balloon 150 could also be used to independently measuresimultaneous esophageal pressure by transmitting the bias balloonpressure from line 154 via line 158 to transducer 160, which may besimilar to transducer 118, which converts the pressure to an electricalsignal which is then transmitted via line 162 to signal processor 164,which may be similar to processor 124, in which the signal is suitablyprocessed and transmitted via line 166 to display 168, which may besimilar to display 142.

The aforesaid U.S. Pat. No. 5,263,485 describes a multi-lumen catheterproviding a first passage for flow communication with a balloon similarto balloon 24 for determining mean left atrial pressure, a secondpassage for serving as a naso-gastric tube, and a third passage whichserves as a transmission passage for an esophageal stethoscope and whichincorporates a temperature sensor. Transmission of heart sounds via thethird passage is facilitated by a plurality of apertures in the cathetertubing for the third passage, and these apertures are covered by aprotective pouch. This pouch or balloon may also serve similarly as biasballoon 150 to eliminate respiratory artifacts by filling it withperhaps 0.1 cc of air for making the required measurements.

As shown in FIGS. 9 and 10, the low frequency oscillationsrepresentative of respiratory artifact decrease in amplitude as thepressure in the balloon 24 increases. In order that the same amplitudeof respiratory wave at each point in time may be supplied to both sidesof the pressure transducer 68 so that effective cancellation ofrespiratory artifact may be achieved, balloons 150 and 24 are bothconnected to gas supply 100 via line 60. Thus, lines 61 and 155 connectline 60 to line 154 for inflation of balloon 150. In order to preventthe cardiac signals from appearing on the bias balloon signal, asuitable low pass filter 157, which may be similar to filter 72, isconnected so that line 61 extends from line 60 to input pressure frompressure source 100 to filter 157, and the output of filter 157, withthe cardiac waves removed, is transmitted via lines 155 and 154 toballoon 150. In accordance with an alternative embodiment (not shown),two separate gas supplies may be provided for balloons 24 and 150 toprevent signal contamination with suitable pressure transducers andelectronic feedback means to automatically maintain the mean pressure inthe bias balloon 150 equal to the mean pressure in the sensing balloon24. In accordance with another alternative embodiment (not shown), twoseparate gas supplies may be provided with a pressure regulator on thebias balloon side which is referenced to the mean sensing balloonpressure and such that cardiac oscillations are not conducted across theregulator.

It should be understood that other means, for example, analog or digitalfiltering techniques applied directly to the absolute balloon pressureto remove low frequency artifacts such as from respiration orperistalsis may be used for deriving wave form 112 from the absoluteballoon pressure, and such other means are meant to come within thescope of the present invention.

The wave form 112 is thus an oscillating signal of varying amplitude ona steady baseline. These oscillations, derived from absolute balloonpressure, are in response to the driving pressure of the left atrium.

By noting the peak resonant amplitude of the wave form 112 (FIG. 11) andcomparing it to the simultaneous mean balloon pressure 110 (FIG. 10),the mean left atrial pressure can be determined. Thus, in accordancewith the oscillometric principle, the mean balloon pressure approximatesthe mean left atrial pressure when the oscillations of wave form 112 areat a peak, i.e., the peak or highest amplitude oscillations in the waveform 112 occur at the time 116 the balloon pressure is equal to meanleft atrial pressure. The mean left atrial pressure is thus determinedfrom the example of FIGS. 9 to 12 to be a pressure, illustrated at 128,of about 3 cm water. It should be understood that pressure 128approximates mean left atrial pressure. To obtain a more precisedetermination of mean left atrial pressure, the pressure 128 must beadjusted for the effects of heart weight, as discussed hereinafter.

It should be recognized that mean left atrial pressure may alternativelybe approximated by reference to the absolute balloon pressure wave form108. Thus, the relatively small amplitude of the high frequencyoscillations on wave form 108 would permit one to estimate the meanballoon pressure from which an estimation of mean left atrial pressuremay be obtained.

It should be understood that it is not essential to the presentinvention that the wave forms in FIGS. 9 to 12 be actually obtained ingraph or tracing form. For example, an electronic peak detector mayalternatively be used to sense the maximum or peak amplitude, andassociated electronics may then determine and display the correspondingmean left atrial pressure in accordance with principles commonly knownto those of ordinary skill in the art to which this invention pertains.

The relaxed diameter of the normal adult esophagus is about 2.5 cm. Theinflated balloon diameter should be less than this in order to avoidstretching the esophagus since, if this were to happen, not all of theballoon pressure would be applied to the left atrial wall with theresult that the balloon pressure at peak oscillation would be higherthan the mean left atrial pressure. In addition, if the balloon is toolarge, its inflation may trigger secondary peristalsis. On the otherhand, if the inflated balloon diameter is too small, it will not be ableto exert adequate pressure against the left atrium during inflation, norwill it have optimal contact area to optimize pulse transmission. Theballoon length should be adequate to provide optimal longitudinalcontact with the left atrium and pulmonary veins in which the meanpressure equals mean left atrial pressure, but should not extend too farbeyond the left atrium where it could pick up pressure artifacts fromthe aorta, pulmonary artery, right ventricle, or lower esophagealsphincter. In accordance with the above requirements, for use in adults,the balloon 24 preferably has an inflated diameter, illustrated at 132in FIG. 2, which is between about 0.8 and 1.5 cm and an inflated length,illustrated at 134 in FIG. 1, which is between about 2 and 4 cm. Morepreferably, the balloon 24 has an inflated diameter 132 of about 1 cmand an inflated length 134 of about 2 to 4 cm., more preferably, about2.5 cm, providing a volume of about 2 milliliters. This diameter stillallows the vertebral column to serve as an anvil since the esophagus isnormally collapsed. For children and neonates the above sizes will besuitably reduced.

Maximum oscillation of balloon pressure may coincidentally occur justbefore the balloon reaches its full volume after which the balloonpressure may rise very sharply, as indicated at 196 in FIG. 10.Sometimes this sharp rise may obscure the point of maximum balloonoscillation. In order to allow better control of balloon pressurefilling for smoother balloon inflation near the point of maximumoscillation, a balloon with an exhaust line for exhausting the balloonoutside the body is described in the aforesaid U.S. Pat. No. 5,263,485for the purpose of slowing such a rapid pressure rise. However, the useof a stepping motor for controlling the balloon filling by a syringe, aspreviously discussed, may desirably eliminate the need for such anexhaust line.

In certain body positions such as supine and semi-recumbent, the heartweight bears on the esophagus. In such a case the balloon pressure 128must be adjusted for the effect of heart weight, as hereinafterdescribed, to obtain a more precise determination of mean left atrialpressure. In other body positions such as standing, sitting, lying onthe side, or prone, the heart weight might not bear on the esophagus,but this will depend on how the heart is suspended in the chest.

The tissue pressure in the chest (mediastinum) reflects the intrapleuralpressure, which is usually subatmospheric at end expiration duringregular breathing when an individual is sitting. Esophageal pressure byitself is considered to approximate intrapleural pressure at a point inthe esophagus away from the weight of the heart. Mean heart weight maybe thought of as a static force, seen best in the supine position, whichcontributes to the local esophageal pressure immediately beneath theheart. Intrapleural pressure and heart weight are additive. The slopechange at point 200 in FIG. 10 is believed to occur when the balloonpressure equals the combined pressure effect of the heart weight and theintrapleural pressure.

The oscillometric theory teaches that a pulsatile structure such as theballoon will resonate maximally when the mean pressure outside thestructure equals the mean pressure inside the structure. As the balloonis inflated with air while behind the heart, the pressure in the balloongradually increases and this pressure increase is transmitted to theadjacent tissues. Given good physical coupling between the balloon andthe left atrial wall, the balloon should drive the tissue pressureadjacent to the left atrial wall higher than the mean left atrialpressure. As the tissue pressure adjacent to the left atrium reachesmean left atrial pressure, the tissue should resonate maximally andcause the balloon to resonate as well. However, at the moment that thisoccurs, the balloon pressure may actually be greater than mean leftatrial pressure because the balloon pressure will include the effect ofheart weight. To determine the heart weight contribution to balloonpressure, it is necessary to know the intrapleural pressure at themoment 200 that the balloon starts to fill. Based on the intrapleuralpressure being believed to be approximately equal to esophageal pressureat some point away from where the heart presses on the esophagus, thispressure may be determined by moving the balloon to this position(perhaps at least about 10 or 11 cm. above the heart), evacuating andthen filling it. During filling, there will be an initial slope changesimilar to slope change 200 which will be approximately the intrapleuralpressure. Alternatively, mean esophageal pressure may be determined byuse of a second balloon whereby the balloon 24 may be kept adjacent theleft atrium. The pressure contribution of the heart weight may becalculated to be the pressure (P1) at the initial slope change 200 asthe balloon fills while behind the heart less the pressure (P2) at theinitial slope change as the balloon fills while away from the heart. Inother words, P1-P2=(pressure due to heart weight+intrapleuralpressure)-intrapleural pressure=pressure due to heart weight. Therefore,to obtain a more precise determination of mean left atrial pressure, thepressure contribution by the heart weight is subtracted from the peakballoon oscillation pressure.

The distance between slope changes at points 200 and 128 in a freeballoon pressure/volume curve is referred to herein as a plateau. It isbelieved that, to insure correct balloon placement and proper pressurecoupling between left atrium and balloon, the peak balloon oscillationpressure must occur within the time frame of the free balloonpressure/volume plateau. Thus, an on-line comparison of free balloon andesophageal balloon curves may be made to allow recognition of inadequatecoupling so that any data obtained thereby can be discarded. The balloondiameter may be increased, such as from perhaps 8 to 9 mm, to obtainadequate coupling when the balloon is properly placed adjacent the leftatrium.

Determination of mean left atrial pressure thus requires making balloonpressure measurements in two locations, which is bothersome. However,the determination of a more clinically useful physiologic value, thetransmural pressure, may be obtained without moving the balloon from itsinitial position beside the left atrium. This value is particularlyimportant because it can influence the degree to which fluid will leavethe pulmonary capillaries and enter the lung tissue, causing pulmonaryedema or "wet lungs." Thus, it allows physicians to more preciselydetermine when a patient could go into pulmonary edema from heartfailure or volume overload, and it also allows an assessment of theeffect of positive end expiratory pressure with ventilated patients.Clinicians are not accustomed to using this pressure because heretoforeit has not been readily available.

Transmural pressure is equal to the mean left atrial pressure minus theintrapleural pressure which is equal to the peak balloon oscillationpressure- (pressure due to heart weight+intrapleuralpressure)-intrapleural pressure!-intrapleural pressure. Thus, transmuralpressure equals peak balloon oscillation pressure-(pressure due to heartweight+intrapleural pressure). As previously discussed, the pressure atslope change point 200 is equal to the pressure due to heart weight plusthe intrapleural pressure. Therefore, the transmural pressure is equalto the peak balloon oscillation pressure 128 less the pressure at slopechange point 200, and both of these values come from the same balloonposition, i.e., adjacent the left atrium. Further, since the balloonneed not be moved away from the heart to measure esophageal pressure asan approximation of intrapleural pressure, this eliminates any concernsabout the validity of esophageal pressure as a measure of intrapleuralpressure, about the optimum position in the esophagus for measuringintrapleural pressure, and about any other factors in or around theesophagus that would distort intrapleural pressure determination.

The method and apparatus of the present invention may be used forproviding precise determination of mean left atrial pressure forpatients connected to respirators. However, when a patient is connectedto a breathing machine which uses positive end expiratory pressure(PEEP), the patient's pulmonary capillary wedge pressure (PCWP) and meanleft atrial pressure (MLAP) may be elevated as a result, since allintra-thoracic structures are exposed to varying degrees to thispressure. Since mean esophageal pressure reflects intra-pleural pressure(a good measure of the pressure environment in the chest), the meanesophageal pressure will provide a measure of the effect of PEEP onthoracic structures. Thus, the mean left atrial transmural pressure, asprovided by the catheter, provides an excellent means to understand thephysiologic and clinical impact of PEEP on the heart and lungs since ittakes into account simultaneous pressure changes induced in both theleft atrium and the esophagus by the imposition of PEEP.

Without wishing to be bound by theory here or elsewhere in thisapplication, it is believed that the balloon best transmits not onlypressures acting on it but also sound when unloaded, i.e., maximum soundenergy may penetrate the balloon wall when it is not in tension (whenthe pressure on opposite sides thereof is balanced). Thus, the amplitudeof heart sounds or any other sounds transmitted through the balloon andtubing is believed to be greatest when the mean balloon pressure equalsthe mean left atrial pressure (including the effect, if any, of heartweight) so that the balloon is unloaded. Accordingly, referring to FIGS.14 and 15, in accordance with the present invention, the balloonpressure may be measured when the amplitude (intensity) of heart sounds,illustrated at 400, or other sound waves (sound pressure level)transmitted by the balloon 24 and tubing 22 is at a peak as anindication (after adjustment, as previously discussed, for the effect,if any, of heart weight) of mean left atrial pressure. Thus, acondenser-type or other suitable microphone, illustrated at 402, issuitably positioned in a suitable housing 404 in an entrance,illustrated at 414, to the tubing 22 to pick up the heart sounds 400,which may then be filtered with a high pass filter, illustrated at 406in FIG. 15, to remove extraneous frequencies less than perhaps about 30Hertz. Alternatively, a band pass filter may be used. Thus, themicrophone 402 is in pressure or flow communication with the balloon 24and tubing 22 for receiving the heart sounds 400 passing along thetubing pathway generally free of interference, and the sounds 400 passthrough the wall of the balloon 24 on their way to the microphone 402.The microphone 402 may, for example, be an Archer Electret PC-mountcondenser microphone element marketed by Radio Shack, a division ofTandy Corp., of Fort Worth, Tex. under its catalog no. 270-090.

The condenser microphone 402 conventionally comprises a pair of spacedfoil diaphragms 408 and 410 with an air space 412 therebetween.Diaphragm 408 extends across and closes the opening to a sound-blockinghousing 416 to receive sound waves 400 passing through entrance 414 fromtubing 22. The spaced diaphragms 408 and 410 act as a capacitor withvibration of diaphragm 408 relative to diaphragm 410 effecting achanging capacitance. Diaphragm 410 is positioned within the housing 416so as to be isolated from the sound so as not to vibrate under theinfluence of the sound waves 400 as does the diaphragm 408.

Typical applications of a condenser microphone require the pressure onthe diaphragms to be equalized. Normally, the pressure changesencountered such as barometric pressure changes or other pressurechanges are relatively small and slow so that very small holes in thecasing 402 and diaphragm 410 need only be provided. These pressureequilibration holes are accordingly sufficiently small that soundpassing into the casing has a very low intensity thus not causing asignificant bias effect while allowing slow pressure equilibration inresponse to slow barometric pressure changes or the like.

The pressure changes within the tubing 22 due to balloon inflation areon the order of 5 or 6 cm. water (5000 to 6000 dynes/cm²) whichrepresents a 1000 to 10,000-fold increase over the pressure changes(perhaps 2 dynes/cm² for the sound of a truck racing its motor or lessthan 0.2 dynes/cm² for heart sounds) typically encountered by themicrophone, and these pressure changes due to balloon inflation occurvery rapidly. If not adequately simultaneously equilibrated, thesepressure changes due to balloon inflation may cause collapse of thecondenser. In order to achieve the desired pressure equilibration forthe large rapid pressure changes encountered in the tubing 22, apressure equilibration hole, illustrated at 418, is drilled to adiameter of perhaps about 0.020 inch, and pressure equilibration holes,illustrated at 420, of a suitable size such as 0.0225 inch are drilledin diaphragm 410 so that the pressure in air space 412 is alsoequalized.

While the hole 418 as well as holes 420 are of a suitable size forpressure equilibration, the hole 418 may be so large as to notsufficiently prevent the passage of sound waves 400 undesirablyresulting in a bias effect. In order to substantially reduce theintensity of sound waves 400 passing through pressure equilibration hole418, in accordance with the present invention a low pass filtercomprising a length of micro-bore tubing 420 having an inside diameterof about 0.15 inch is suitably connected to the hole 418. The length ofthe tubing 420 required to provide adequate pressure equilibration tothe microphone yet block the passage of sound was found empirically tobe about 6 inches. The tubing 420 is desirably composed of a rigidmaterial such as, for example, polypropylene or a fine glass tube, whichsound does not penetrate well.

The balloon and heart pressure wave forms may typically have frequenciesin the range of 3 to 9 Hz. In contrast, the frequency of the sound waves400 may be in the range of 30 to 300 Hz. The microphone 402 is tuned bymeans of the length of tubing 420 to allow the low frequency pressurechanges to equilibrate across the body of the microphone 402 whilepreventing or substantially retarding the much higher sound frequenciesfrom equilibrating. The lower frequency air pressure changes mayaccordingly be transmitted with fidelity through the length of thetubing 420, while the high frequency heart sounds 400 may be attenuatedresulting in a loss of amplitude to perhaps 1/5 of the originalamplitude. Such weakened sound waves passing to the diaphragm 410 shouldnot significantly affect the microphone output. For example, anamplitude of 10 acting on the diaphragm 408 may result in a outputamplitude of 8, which is considered to be suitable for obtaining thedesired relative sound intensity level to a predetermined base line sothat a smooth curve with a pronounced peak may be seen.

For example, for the Radio Shack microphone discussed above, themicro-bore tubing may have a length of perhaps about 6 inches and aninner diameter of perhaps about 0.015 inch. The tubing may, for example,be PE20 low density polyethylene micro-bore tubing manufactured by ClayAdams Intramedic and available from Thomas Scientific of 99 High HillRoad, P.O. Box 99, Swedesboro, N.J. 08085 as featured in the ThomasScientific catalog of 1991-1992 on page 1364 (catalog no. 9565-S16). Thetubing is coiled up as illustrated in FIG. 14 to fit within the housing404 and installed, for example, by means of a 1/4 inch long 25 gagehypodermic stainless steel tube inserted in a 0.02 inch (no. 76 drill)hole in housing 416 and epoxyed thereto to prevent leakage, and thetubing 420 is fit over the stainless steel tube. It should of course beunderstood that the tubing may be installed in various other ways andother suitable low pass filters may be provided. The tuned microphonethus equilibrates rapidly to the high amplitude low frequency ambientpressure changes but does not equilibrate significantly to very lowamplitude, high frequency sound components. Therefore, it can suitablypick up the sound components as desired. This would be the case fordynamic and piezo-electric as well as condenser microphones.

The microphone output may be suitably amplified and recorded for use inobtaining a determination of transmural pressure or other pressureassociated with the left atrium. However, in order to obtain a moreeasily usable representation of the sound, referring to FIG. 15, themicrophone output is passed through a suitable noise or sound intensitymeter 422 in which a decibel equivalent of the sound output isoutputted. This decibel equivalent is then filtered by means of filter406 which removes respiratory frequencies and the like below about 30Hz. The filtered signal is then passed through a suitable exponentialamplifier 424 where it is exponentially amplified to obtain a morepronounced peak. The filtered and amplified signal may then be recordedon a suitable recorder 426.

FIG. 16 shows a tracing 428 similar to that of FIG. 9 of the absoluteballoon pressure from the esophageal balloon 24 as it is filled, using aCobe CDX III transducer. The processes of filling the balloon andmeasuring balloon pressure may be similar to those described withreference to FIGS. 1 to 13. The tracings in FIGS. 16, 17, and 18 occurover the same period of time, as indicated by time line 430. Verticalline 432 in each of FIGS. 16, 17, and 18 represents the same point intime. Tracing 434 in FIG. 17 is the output from the previously describedElectret microphone 402 that has been processed through a 10 to 40 Hzband-pass filter. Tracing 436 in FIG. 18 is a steady baselineoscillometric signal from the balloon 24 which is similarly derived asthe signal 112 shown in FIG. 11. FIG. 18 shows that the peak resonantamplitude of the balloon pressure signal occurs at time 432. FIG. 17shows that the intensity (amplitude) of the sound wave 400 has a peakapproximately at time 432. Thus, tracing 436 confirms that a tracing 434of sound waves transmitted through the balloon 24 may also be used toobtain a determination of mean left atrial pressure or other pressureassociated therewith. Thus, tracings 434 and 436 each demonstrate a meanleft atrial pressure at point 438, assuming no effect by heart weight.

A method for positioning the balloon 24 adjacent the left atrium may beby the use of an esophageal mapping technique wherein the inflatedballoon is lowered to the stomach then slowly pulled up the esophagus.This technique involves locating the second harmonic of the heart rate,i.e., pulse rate and looking for the peak amplitude of the secondharmonic as the balloon is slowly pulled up. The balloon is consideredto be approximately at the position of the left atrium when the peakamplitude or peak power of the second harmonic is greatest. Since thefirst harmonic is typically about 1 Hertz, the second harmonic wouldtypically be about 2 Hertz. However, since the heart rate will vary indifferent individuals, the heart rate and consequently the secondharmonic should be known before this technique is used. The secondharmonic may be found by using the signal spectrum of the fast Fouriertransform, a commonly known mathematical technique, of the balloonpressure signal, using principles commonly known to those of ordinaryskill in the art to which this invention pertains. The second harmonicmay alternatively be found by other suitable methods such as by use of adigital or analog band pass filter. Thus, by looking for the secondharmonic instead of the first harmonic, one may be confident of findingthe left atrial component. Of course, the balloon may be positioned bythe use of other suitable methods.

During treatment of patients, it may be desirable to insert in theesophagus instruments other than the previously discussedballoon-containing catheter, and it may be necessary to insert suchadditional instruments to extend beyond the position of the balloon. Forexample, it may be necessary to insert a naso-gastric tube for providingfluids to or removing fluids from the stomach for feeding or suction.However, by being disposed to lie between the balloon and the esophagealwall, such a tube may undesirably interfere with pressure transmissionbetween the esophageal wall and the balloon for determining mean leftatrial pressure.

In order to prevent such an additional instrument from interfering withthe balloon-esophagus interface, a naso-gastric tube or other elongatemeans extending beyond the balloon is caused to pass centrally of theballoon so that the balloon surrounds the tube, as discussed more fullyin the aforesaid U.S. Pat. No. 5,263,485.

It should be understood that while the present invention has beendescribed in detail herein, the invention can be embodied otherwisewithout departing from the principles thereof. Such other embodimentsare meant to come within the scope of the present invention as definedby the appended claims.

What is claimed is:
 1. Apparatus for determining a mean pressure from asource within a body comprising a balloon positionable within the bodyadjacent the source, means for inflating said balloon, means fordetecting and determining intensity of a sound wave from said sourceafter the sound wave is transmitted through said balloon, and means for,determining the balloon pressure when the intensity of the sound waveis, after the sound wave is transmitted through said balloon, at a peak.2. Apparatus according to claim 1 wherein said detecting and determiningmeans comprises a microphone for receiving and providing an output ofthe sound wave after it is transmitted through said balloon. 3.Apparatus according to claim 2 wherein said microphone is disposed to bein pressure communication with said balloon, said microphone comprisingmeans for equilibrating balloon pressure changes while preventing thesound wave intensity from significantly equilibrating.
 4. Apparatusaccording to claim 3 wherein said microphone is a condenser microphonewhich has a pair of diaphragms acting as a capacitor, housing means forsound isolating one of said diaphragms, low pass filter means in saidhousing means for equilibrating balloon pressure changes, and means forequalizing pressure on both sides of said one diaphragm.
 5. Apparatusaccording to claim 4 wherein said low pass filter means comprises alength of tubing connected to said housing to provide communicationbetween the interior and exterior of said housing, said tubing selectedto have a length and bore diameter which equilibrates balloon pressurechanges while preventing the sound wave intensity from significantlyequilibrating.
 6. Apparatus according to claim 5 wherein said tubing iscomposed of a rigid material whereby to prevent penetration of soundthrough a wall of said tubing.
 7. Apparatus according to claim 1 whereinsaid means for measuring the balloon pressure comprises means formeasuring the mean balloon pressure when the intensity of a sound waveis, after the sound wave is transmitted through said balloon, at a peak.8. Apparatus comprising a catheter which includes a balloon and isinsertable into an esophagus for positioning said balloon adjacent theleft atrium, means for inflating said balloon, means for detecting anddetermining intensity of heart sounds from the left atrium after theheart sounds are transmitted through said balloon, and means fordetermining the balloon pressure when the intensity of the heart sounds,after they are transmitted through said balloon, is at a peak. 9.Apparatus according to claim 8 wherein said balloon has an inflateddiameter which is between about 0.8 and 1.5 cm.
 10. Apparatus accordingto claim 8 further comprising means for adjusting the measured balloonpressure for the effect of heart weight.
 11. Apparatus according toclaim 8 wherein said means for measuring the balloon pressure comprisesmeans for measuring the mean balloon pressure when the intensity of asound wave is, after the sound wave is transmitted through said balloon,at a peak.
 12. Apparatus according to claim 11 wherein said catheterincludes means defining a balloon pressurization line and saidmicrophone is disposed in pressure communication with said balloonpressurization line, said microphone comprising means for equilibratingballoon pressure changes while preventing the intensity of the heartsounds from significantly equilibrating.
 13. Apparatus according toclaim 12 wherein said microphone is a condenser microphone which has apair of diaphragms acting as a capacitor, housing means for soundisolating one of said diaphragms, low pass filter means in said housingmeans for equilibrating balloon pressure changes, and means forequalizing pressure on both sides of said one diaphragm.
 14. Apparatusaccording to claim 13 wherein said low pass filter means comprises alength of tubing connected to said housing to provide communicationbetween the interior and exterior of said housing, said tubing selectedto have a length and bore diameter which equilibrates balloon pressurechanges while preventing the intensity of the heart sounds fromsignificantly equilibrating.
 15. Apparatus according to claim 14 whereinsaid tubing is composed of a rigid material whereby to preventpenetration of sound through a wall of said tubing.
 16. Apparatusaccording to claim 8 wherein said detecting and determining meanscomprises a microphone for receiving and providing an output of theheart sounds after they are transmitted through said balloon.
 17. Amethod of determining a mean pressure from a source within a bodycomprising the steps of:a. positioning a balloon within the bodyadjacent the source; (b) inflating the balloon; and (c) determiningintensity of a sound wave from the source after the sound wave istransmitted through the balloon, and determining the balloon pressurewhen the intensity of the sound wave is, after the sound wave istransmitted through the balloon, at a peak.
 18. A method according toclaim 17 comprising positioning the balloon between the source and amember such that the member acts as acts as an anvil for the sourcepressure acting on the balloon.
 19. A method according to claim 17comprising disposing a microphone having a pair of diaphragms acting asa capacitor and one of which is sound isolated in pressure communicationwith the balloon, and equilibrating balloon pressure changes acting onthe diaphragms while preventing the sound wave intensity fromsignificantly equilibrating.
 20. A method according to claim 19comprising connecting tubing to the housing to provide communicationbetween the interior and exterior of the housing, and selecting thelength and bore diameter of the tubing to equilibrate balloon pressurechanges to the diaphragms while preventing the sound wave intensity fromsignificantly equilibrating.
 21. A method according to claim 20 furthercomprising selecting the tubing to be composed of a rigid material toprevent penetration of sound through a wall of the tubing.
 22. A methodof determining a mean pressure from a source within a body comprisingthe steps of:a. positioning a balloon within the body adjacent thesource; b. inflating the balloon; and c. determining intensity of asound wave from the source after the sound wave is transmitted throughthe balloon, and determining the mean balloon pressure when theintensity of the sound wave is, after the sound wave is transmittedthrough the balloon, at a peak.
 23. A method of determining mean leftatrial pressure comprising the steps of:a. inserting a catheterincluding a balloon into an esophagus of a subject; b. positioning theballoon adjacent the left atrium; c. inflating the balloon; and d.determining intensity of heart sounds from the left atrium after theheart sounds are transmitted through the balloon, and determining theballoon pressure when the intensity of the heart sounds after they aretransmitted through the balloon is at a peak.
 24. A method according toclaim 23 further comprising selecting the balloon to have an inflateddiameter which is between about 0.8 and 1.5 cm.
 25. A method accordingto claim 23 wherein the step of measuring the balloon pressure comprisesmeasuring the mean balloon pressure when the intensity of heart soundsafter they are transmitted through the balloon is at a peak.
 26. Amethod according to claim 23 comprising disposing a microphone having apair of diaphragms acting as a capacitor and one of which is soundisolated in pressure communication with the balloon, and equilibratingballoon pressure changes acting on the diaphragms while preventing thesound wave intensity from significantly equilibrating.
 27. A methodaccording to claim 26 comprising connecting tubing to the housing toprovide communication between the interior and exterior of the housing,and selecting the length and bore diameter of the tubing to equilibrateballoon pressure changes to the diaphragms while preventing the soundwave intensity from significantly equilibrating.
 28. A method accordingto claim 27 further comprising selecting the tubing to be composed of arigid material to prevent penetration of sound through a wall of thetubing.
 29. A method according to claim 23 further comprising adjustingthe measured balloon pressure for the effect of heart weight.
 30. Amethod according to claim 29 wherein the step of adjusting the measuredballoon pressure comprises determining the difference between balloonpressures at which balloon volume begins to increase greatly relative toincrease in balloon pressure while the balloon is inflated whileadjacent the left atrium and while a balloon is inflated while at adistance of at least about 10 cm. from the heart respectively andsubtracting said difference from the measured balloon pressure when theintensity of heart sound is at a peak.